Targeting neurodegenerative diseases: Drug discovery in a challenging arena

Neurodegenerative diseases represent one of the health care community's truly unmet medical needs. They can be loosely classified into two categories, acute and chronic. One of the best known chronic neurodegenerative diseases, Alzheimer's disease, represents a serious health care problem that may well exceed the limits of current fiscal and care giver resources. No disease- modifying therapeutic agents have been identified, and the few available symptomatic treatments possess limitations in their duration of action and side effects. Despite decades of drug discovery research and numerous clinical trials, no truly effective treatment for stroke, the most prevalent acute neurodegenerative disease, has been identified. This article summarizes two recent drug discovery projects, one targeting Alzheimer's disease and the other targeting ischemic stroke. Both projects involved design, synthesis, and biological evaluation of a novel series of heterocyclic derivatives.